US9403770B2 - Process for preparing fexofenadine - Google Patents

Process for preparing fexofenadine Download PDF

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Publication number
US9403770B2
US9403770B2 US12/374,539 US37453907A US9403770B2 US 9403770 B2 US9403770 B2 US 9403770B2 US 37453907 A US37453907 A US 37453907A US 9403770 B2 US9403770 B2 US 9403770B2
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process according
compound
formula
fexofenadine
base
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US20110190504A1 (en
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Giorgio Bertolini
Maurizio Gallina
Giuseppe Motta
Domenico Vergani
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Curia Italy SRL
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Euticals SpA
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
    • C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
    • C07D211/08—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms
    • C07D211/18—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms
    • C07D211/20—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by singly bound oxygen or sulphur atoms
    • C07D211/22—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by singly bound oxygen or sulphur atoms by oxygen atoms

Definitions

  • Process for preparing fexofenadine comprising the hydrolysis of 4-[4-[4-(hydroxydiphenylmethyl)-1-piperidyl]-1-oxobutyl]- ⁇ , ⁇ -dimethylbenzeneacetic acid-alkyl ester to 4-[4-[4-(hydroxydiphenylmethyl)-1-piperidyl]-1-oxobutyl]- ⁇ , ⁇ -dimethylbenzeneacetic acid which is catalytically hydrogenated as fexofenadine carboxylate salt.
  • the present invention concerns a process for preparing fexofenadine, the formula (I) of which is shown below:
  • R is an alkyl group, in a mixture of water and optionally an organic solvent, in the presence of a base by obtaining the carboxylate salt of 4-[4-[4-(hydroxidiphenylmethyl)-1-piperidyl]-1-oxobutyl]- ⁇ , ⁇ -dimethylbenzeneacetic acid, shown below as formula (III),
  • M+ is the cation of the carboxylate salt (or, in other words, the cation of the base used for the hydrolysis), which is directly reduced as carboxylate in a basic environment with hydrogen in the presence of a suitable catalyst to give the carboxylate of fexofenadine, which is precipitated by neutralisation of the solution.
  • R is an alkyl group, preferably a C 1 -C 4 alkyl group, still more preferably methyl, is dissolved or suspended in a mixture of organic solvent and water, in the presence of a base, or in water and base only, and hydrolysed under stirring at a temperature comprised between 0° C. and the reflux temperature of the mixture.
  • the organic solvent is preferably a polar solvent, normally of a protic type, preferably a C 1 -C 4 alcohol, still more preferably methanol.
  • the base is preferably of an inorganic nature, such as, for example, the hydroxide of an alkaline or alkaline-earth metal, still more preferably NaOH.
  • Said organic solvent when used, is present in ratios in the range of 0.25-16 volumes in relation to water; or said mixture of water and organic solvent is preferably present in 6-7 volumes in relation to compound II; the base, in turn, is preferably used in molar excess in relation to the compound of formula II, preferably with a molar ratio from 3 to 5.
  • M+ is the cation of the carboxylate salt, preferably Na + .
  • a suitable metallic-type hydrogenation catalyst is added to the system thus obtained, preferably selected from suitably supported palladium, platinum, or ruthenium (preferably palladium on carbon) and is hydrogenated at a temperature between 0° C. and the boiling point of the solvent at a pressure in the range of 1-100 bar, preferably 1-10 bar.

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Hydrogenated Pyridines (AREA)
  • Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
  • Saccharide Compounds (AREA)
  • Compounds Of Iron (AREA)
US12/374,539 2006-07-27 2007-07-25 Process for preparing fexofenadine Expired - Fee Related US9403770B2 (en)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
IT001492A ITMI20061492A1 (it) 2006-07-27 2006-07-27 Processo per la preparazione di fexofenadina.
ITMI2006A1492 2006-07-27
ITMI2006AO01492 2006-07-27
PCT/IT2007/000525 WO2008012858A1 (en) 2006-07-27 2007-07-25 Process for preparing fexofenadine

Publications (2)

Publication Number Publication Date
US20110190504A1 US20110190504A1 (en) 2011-08-04
US9403770B2 true US9403770B2 (en) 2016-08-02

Family

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US12/374,539 Expired - Fee Related US9403770B2 (en) 2006-07-27 2007-07-25 Process for preparing fexofenadine

Country Status (10)

Country Link
US (1) US9403770B2 (ko)
EP (1) EP2046743B1 (ko)
JP (1) JP5196501B2 (ko)
KR (1) KR101413877B1 (ko)
CN (1) CN101522619B (ko)
AT (1) ATE488502T1 (ko)
DE (1) DE602007010638D1 (ko)
ES (1) ES2356269T3 (ko)
IT (1) ITMI20061492A1 (ko)
WO (1) WO2008012858A1 (ko)

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN106699559B (zh) * 2015-11-12 2021-04-06 浙江九洲药业股份有限公司 一种洛索洛芬钠的制备工艺
CN107782804B (zh) * 2016-08-25 2020-11-13 人福普克药业（武汉）有限公司 检测盐酸非索非那定样品中有关物质的方法

Citations (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4254129A (en) 1979-04-10 1981-03-03 Richardson-Merrell Inc. Piperidine derivatives
US5136070A (en) * 1991-12-23 1992-08-04 Dow Corning Corporation Sodium borohydride catalyzed disproportionation of cycloorganosilanes
US5663412A (en) * 1993-06-24 1997-09-02 Albany Molecular Research, Inc. Aromatic ketones
US20020111513A1 (en) 1998-07-02 2002-08-15 Ayers Timothy A. Novel antihistaminic piperidine derivatives and intermediates for the preparation thereof
US20030105329A1 (en) 2001-06-15 2003-06-05 Collin Schroeder Process for the production of piperidine derivatives
US20030171590A1 (en) 1995-12-21 2003-09-11 D'ambra Thomas E. Process for production of piperidine derivatives
US20030220496A1 (en) 1993-06-25 2003-11-27 Merrell Pharmaceuticals, Inc. Novel intermediates useful for the preparation of antihistaminic piperidine derivatives
US20050282860A1 (en) * 2004-06-08 2005-12-22 Dipharma S.P.A. Fexofenadine polymorphs and process for the preparation thereof
WO2006037042A1 (en) 2004-09-28 2006-04-06 Teva Pharmaceutical Industries Ltd. Fexofenadine crystal form and processes for its preparation thereof

Family Cites Families (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4254130A (en) * 1979-04-10 1981-03-03 Richardson-Merrell Inc. Piperidine derivatives
WO1993021156A1 (en) * 1992-04-10 1993-10-28 Merrell Dow Pharmaceuticals Inc. 4-diphenylmethyl piperidine derivatives and process for their preparation
US20020007068A1 (en) * 1999-07-16 2002-01-17 D'ambra Thomas E. Piperidine derivatives and process for their production
US6153754A (en) * 1995-12-21 2000-11-28 Albany Molecular Research, Inc. Process for production of piperidine derivatives
ITRM20010260A1 (it) * 2001-05-17 2002-11-18 Dinamite Dipharma S P A In For Processo per la preparazione della fexofenadina o acido 4 1-idrossi-4-4- (idrossidifenilmetil)-1-piperidinil|-butil|-alfa,alfa-dimetilbenz

Patent Citations (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4254129A (en) 1979-04-10 1981-03-03 Richardson-Merrell Inc. Piperidine derivatives
US5136070A (en) * 1991-12-23 1992-08-04 Dow Corning Corporation Sodium borohydride catalyzed disproportionation of cycloorganosilanes
US5663412A (en) * 1993-06-24 1997-09-02 Albany Molecular Research, Inc. Aromatic ketones
US20030220496A1 (en) 1993-06-25 2003-11-27 Merrell Pharmaceuticals, Inc. Novel intermediates useful for the preparation of antihistaminic piperidine derivatives
US20030171590A1 (en) 1995-12-21 2003-09-11 D'ambra Thomas E. Process for production of piperidine derivatives
US20020111513A1 (en) 1998-07-02 2002-08-15 Ayers Timothy A. Novel antihistaminic piperidine derivatives and intermediates for the preparation thereof
US20030105329A1 (en) 2001-06-15 2003-06-05 Collin Schroeder Process for the production of piperidine derivatives
US20050282860A1 (en) * 2004-06-08 2005-12-22 Dipharma S.P.A. Fexofenadine polymorphs and process for the preparation thereof
EP1614681A1 (en) 2004-06-08 2006-01-11 Dipharma S.p.A. Fexofenadine polymorphs and process for the preparation thereof
WO2006037042A1 (en) 2004-09-28 2006-04-06 Teva Pharmaceutical Industries Ltd. Fexofenadine crystal form and processes for its preparation thereof
US20060148851A1 (en) * 2004-09-28 2006-07-06 Shlomit Wizel Fexofenadine crystal form and processes for its preparation thereof

Non-Patent Citations (6)

* Cited by examiner, † Cited by third party
Title
Aldrich catalog, p. 1-2 (2012). *
Carbonyl reduction, Wikepedia p. 1-2 (2015). *
Ivashchenko et al. "Preparation, . . . " WJNSE v.2, p. 117-125 (2012). *
Tiedtke et al. "Chemicals influencing . . . " 13th Ethylene producers' conference, v.10 p. 1-21 (2001). *
Wizel "Preparation of a polymorphic . . . " CA144:350552 (2006). *
Yabe et al. "New aspect of . . . " Cat. Sci. Tech. (2013) p. 1-10, accepted manuscript (2013). *

Also Published As

Publication number Publication date
ITMI20061492A1 (it) 2008-01-28
KR20090034905A (ko) 2009-04-08
ES2356269T3 (es) 2011-04-06
JP2009544691A (ja) 2009-12-17
EP2046743B1 (en) 2010-11-17
CN101522619B (zh) 2012-01-04
WO2008012858A1 (en) 2008-01-31
ATE488502T1 (de) 2010-12-15
DE602007010638D1 (de) 2010-12-30
KR101413877B1 (ko) 2014-06-30
CN101522619A (zh) 2009-09-02
US20110190504A1 (en) 2011-08-04
EP2046743A1 (en) 2009-04-15
JP5196501B2 (ja) 2013-05-15

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